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30-504: CredibleMeds is an online database launched in 2009 of information regarding serious drug-drug interactions associated with QT prolongation or the potentially lethal arrhythmia , torsades de pointes (TdP) . It also assists with measurement of the quality of healthcare delivery for the Centers for Medicare and Medicaid Services , and aids in the management of patients with inherited channelopathies . The overall goal of CredibleMeds

60-555: A device to increase their shows' ratings. Characters may be antagonists without being evil – they may simply be injudicious and unlikeable for the audience. In some stories, such as The Catcher in the Rye , almost every character other than the protagonist may be an antagonist. Another example of this occurring is through Javert in Victor Hugo's Les Misérables , in which Javert displays no malicious intent, but instead represents

90-436: A drug is metabolized by a CYP450 enzyme and drug B blocks the activity of these enzymes, it can lead to pharmacokinetic alterations. A. This alteration results in drug A remaining in the bloodstream for an extended duration, and eventually increase in concentration. In some instances, the inhibition may reduce the therapeutic effect, if instead the metabolites of the drug is responsible for the effect. Compounds that increase

120-428: A harmful interaction, including drugs with a narrow therapeutic index , where the difference between the effective dose and the toxic dose is small. The drug digoxin is an example of this type of drug. Risks are also increased when the drug presents a steep dose-response curve , and small changes in the dosage produce large changes in the drug's concentration in the blood plasma. As of 2008, among adults in

150-554: A high bioavailability . For this reason its administration is contraindicated in enteral feeding . Some drugs also alter absorption by acting on the P-glycoprotein of the enterocytes . This appears to be one of the mechanisms by which grapefruit juice increases the bioavailability of various drugs beyond its inhibitory activity on first pass metabolism . Drugs also may affect each other by competing for transport proteins in plasma , such as albumin . In these cases

180-570: A release of catecholamines , triggering symptoms that hint the organism to take action, like consuming sugary foods. If a patient is on insulin , which reduces blood sugar, and also beta-blockers , the body is less able to cope with an insulin overdose. Pharmacokinetics is the field of research studying the chemical and biochemical factors that directly affect dosage and the half-life of drugs in an organism, including absorption, transport, distribution, metabolism and excretion. Compounds may affect any of those process, ultimately interfering with

210-466: Is often used by an author to create conflict within a story. This is merely a convention, however. An example in which this is reversed can be seen in the character Macduff from Macbeth , who is arguably morally correct in his desire to fight the tyrant Macbeth , the protagonist. Examples from television include J.R. Ewing ( Larry Hagman ) from Dallas and Alexis Colby ( Joan Collins ) from Dynasty . Both became breakout characters used as

240-464: Is opposite to that of the main drug. These may be c ompetitive antagonists , if they compete with the main drug to bind with the receptor. or u ncompetitive antagonists, when the antagonist binds to the receptor irreversibly. The drugs can be considered heterodynamic competitors, if they act on distinct receptor with similar downstream pathways . The interaction my also occur via signal transduction mechanisms. For example, low blood glucose leads to

270-454: Is presented as the main enemy or rival of the protagonist . The English word antagonist comes from the Greek ἀνταγωνιστής – antagonistēs , "opponent, competitor, villain, enemy, rival," which is derived from anti- ("against") and agonizesthai ("to contend for a prize"). The antagonist is commonly positioned against the protagonist and their world order. While narratives often portray

300-411: Is the case for oral anticoagulants and avocado . The formation of non-absorbable complexes may occur also via chelation , when cations can make certain drugs harder to absorb, for example between tetracycline or the fluoroquinolones and dairy products, due to the presence of calcium ions . . Other drugs bind to proteins. Some drugs such as sucralfate bind to proteins, especially if they have

330-821: Is to support efforts to improve the safe use of medicines. The Arizona Center for Education and Research on Therapeutics (AZCERT) maintains the CredibleMeds database. Founded in 2000 at the University of Arizona as part of a network of 14 federally-funded CERTs, AZCERT became a separate non-profit corporation in 2012 funded by the US Food and Drug Administration (FDA) , research grants , and charitable contributions . AZCERT focuses on drugs and drug–drug interactions , especially those that cause QT prolongation and Torsades de Pointes (TdP) arrhythmia , and provides its research and its lists of drugs free of charge to

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360-582: The United States , especially in Europe , Japan , and Canada . In addition to their use to inform healthcare decision-making, CredibleMeds’ lists of drugs have been used in research published in more than 50 scientific articles. Drug interaction Interactions may occur by simultaneous targeting of receptors , directly or indirectly. For example, both Zolpidem and alcohol affect GABA A receptors , and their simultaneous consumption results in

390-401: The United States of America older than 56, 4% were taking medication and/ or supplements that put them at risk of a major drug interaction. Potential drug-drug interactions have increased over time and are more common in the less-educated elderly even after controlling for age, sex, place of residence, and comorbidity . Antagonist An antagonist is a character in a story who

420-442: The precipitation of thiopentone. Pharmacodynamic interactions are the drug–drug interactions that occur at a biochemical level and depend mainly on the biological processes of organisms. These interactions occur due to action on the same targets; for example, the same receptor or signaling pathway . Pharmacodynamic interactions can occur on protein receptors . Two drugs can be considered to be homodynamic , if they act on

450-442: The absorption of other drugs such as zalcitabine , tipranavir and amprenavir . The opposite is more common, with, for example, the antacid cimetidine stimulating the absorption of didanosine . Some resources describe that a gap of two to four hours between taking the two drugs is needed to avoid the interaction. Factors such as food with high-fat content may also alter the solubility of drugs and impact its absorption. This

480-471: The appearance of interactions include factors such as old age . This is where human physiology changing with age may affect the interaction of drugs. For example, liver metabolism, kidney function, nerve transmission, or the functioning of bone marrow all decrease with age. In addition, in old age, there is a sensory decrease that increases the chances of errors being made in the administration of drugs. The elderly are also more vulnerable to polypharmacy , and

510-410: The cause of the protagonist's main problem, or lead a group of characters against the protagonist; in comedies, they are usually responsible for involving the protagonist in comedic situations. Author John Truby argues that a true opponent not only wants to prevent the hero from achieving his desire but is competing with the hero for the same goal. According to John Truby, "It is only by competing for

540-541: The drug that arrives first binds with the plasma protein, leaving the other drug dissolved in the plasma, modifying its expected concentration. The organism has mechanisms to counteract these situations (by, for example, increasing plasma clearance ), and thus they are not usually clinically relevant. They may become relevant if other problems are present, such as issues with drug excretion. Many drug interactions are due to alterations in drug metabolism . Further, human drug-metabolizing enzymes are typically activated through

570-454: The efficiency of the enzymes, on the other hand, may have the opposite effect and increase the rate of metabolism. An example of this is shown in the following table for the CYP1A2 enzyme, showing the substrates (drugs metabolized by this enzyme) and some inductors and inhibitors of its activity: Some foods also act as inductors or inhibitors of enzymatic activity. The following table shows

600-406: The engagement of nuclear receptors . One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases . Cytochrome P450 is a very large family of haemoproteins (hemoproteins) that are characterized by their enzymatic activity and their role in the metabolism of a large number of drugs. Of the various families that are present in humans,

630-589: The flux of drugs in the human body , increasing or reducing drug availability. Drugs that change intestinal motility may impact the level of other drugs taken. For example, prokinetic agents increase the intestinal motility , which may cause drugs to go through the digestive system too fast, reducing absorption. The pharmacological modification of pH can affect other compounds. Drugs can be present in ionized or non-ionized forms depending on pKa , and neutral compounds are usually better absorbed by membranes. Medication like antacids can increase pH and inhibit

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660-403: The more drugs a patient takes, the higher is the chance of an interaction. Genetic factors may also affect the enzymes and receptors, thus altering the possibilities of interactions. Patients with hepatic or renal diseases already may have difficulties metabolizing and excreting drugs, which may exacerbate the effect of interactions. Some drugs present an intrinsic increased risk for

690-1551: The most common: Drugs tightly bound to proteins (i.e. not in the free fraction ) are not available for renal excretion . Filtration depends on a number of factors including the pH of the urine. Drug interactions may affect those points. Herb-drug interactions are drug interactions that occur between herbal medicines and conventional drugs. These types of interactions may be more common than drug-drug interactions because herbal medicines often contain multiple pharmacologically active ingredients, while conventional drugs typically contain only one. Some such interactions are clinically significant , although most herbal remedies are not associated with drug interactions causing serious consequences. Most catalogued herb-drug interactions are moderate in severity. The most commonly implicated conventional drugs in herb-drug interactions are warfarin , insulin , aspirin , digoxin , and ticlopidine , due to their narrow therapeutic indices . The most commonly implicated herbs involved in such interactions are those containing St. John’s Wort , magnesium, calcium, iron, or ginkgo . Examples of herb-drug interactions include, but are not limited to: The mechanisms underlying most herb-drug interactions are not fully understood. Interactions between herbal medicines and anticancer drugs typically involve enzymes that metabolize cytochrome P450 . For example, St. John's Wort has been shown to induce CYP3A4 and P-glycoprotein in vitro and in vivo. The factors or conditions that predispose

720-477: The most interesting in this respect are the 1, 2 and 3, and the most important enzymes are CYP1A2 , CYP2C9 , CYP2C19 , CYP2D6 , CYP2E1 and CYP3A4 . The majority of the enzymes are also involved in the metabolism of endogenous substances, such as steroids or sex hormones , which is also important should there be interference with these substances. The function of the enzymes can either be stimulated ( enzyme induction ) or inhibited ( enzyme inhibition ). If

750-732: The overstimulation of the receptor, which can lead to loss of consciousness. When two drugs affect each other, it is a drug–drug interaction (DDI) . The risk of a DDI increases with the number of drugs used. A large share of elderly people regularly use five or more medications or supplements, with a significant risk of side-effects from drug–drug interactions. Drug interactions can be of three kinds: It may be difficult to distinguish between synergistic or additive interactions, as individual effects of drugs may vary. Direct interactions between drugs are also possible and may occur when two drugs are mixed before intravenous injection . For example, mixing thiopentone and suxamethonium can lead to

780-552: The protagonist as a hero and the antagonist as a villain , like Harry Potter and Lord Voldemort in Harry Potter , the antagonist does not always appear as the villain. In some narratives, like Light Yagami and L in Death Note , the protagonist is a villain and the antagonist is an opposing hero. Antagonists are conventionally presented as making moral choices less savory than those of protagonists. This condition

810-549: The public, healthcare providers , and researchers for personal, professional, and non-commercial purposes. To maintain the independence of its work, AZCERT does not receive funding from companies that have a commercial interest in medications. AZCERT developed the Adverse Drug Event Causality Analysis (ADECA) to evaluate drugs for their risk of causing QT prolongation and TdP. As part of its ADECA reviews, AZCERT includes drugs marketed outside

840-418: The rigid and inflexible application of the law, even when it leads to moral and ethical dilemmas. An aspect or trait of the protagonist may be considered an antagonist, such as morality or indecisiveness. An antagonist is not always a person or people. In some cases, an antagonist may be a force, such as a tidal wave that destroys a city; a storm that causes havoc; or even a certain area's conditions that are

870-406: The root cause of a problem. An antagonist may or may not create obstacles for the protagonist. Societal norms or other rules may also be antagonists. An antagonist is used as a plot device, to set up conflicts, obstacles, or challenges for the protagonist. Though not every story requires an antagonist, it often is used in plays to increase the level of drama. In tragedies, antagonists are often

900-409: The same receptor. Homodynamic effects include drugs that act as (1) pure agonists , if they bind to the main locus of the receptor , causing a similar effect to that of the main drug, (2) partial agonists if, on binding to a secondary site, they have the same effect as the main drug, but with a lower intensity and (3) antagonists , if they bind directly to the receptor's main locus but their effect

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